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Photon echo techniques are difficult to implement in the quantum regime due to coherent and spontaneous emission noise. Here, the authors propose a low-noise photon-echo quantum memory approach based on all-optical control in a four-level system, and demonstrate it using a Eu3+:Y2SiO5 crystal.

Abstract Lack of adequate effector T cells infiltrated in tumor is one of the main problems in the failure of immune checkpoint blockade therapy (ICBT). Photodynamic therapy (PDT) induced acute inflammation can sensitize tumors and activate T cells, thus assisting immune checkpoint inhibitors (ICI) against tumor growth and metastasis. T cells maturation and activation lag 3 to 7 days behind PDT. However, such timing in the combination therapy of ICI and PDT is commonly ignored in designing numerous multi‐functional integrated nanomedicines. Herein, the authors illustrate that intervention timing of ICI after PDT affects the anti‐tumor efficacy. A tumor‐targeting nanomedicine is prepared by encapsulating indocyanine green into CD44 specifically binding material, a hyaluronic acid conjugated lipid poly(ethylene glycol). The PDT nanomedicine is designed to induce a robust immune response in tumor. The optimal group (Combo‐STAR), ICI gave 5 days after PDT, significantly suppresses local tumor growth and eliminates metastasis. What should be highlighted is the time point of administration because if ICI is given too early, T cells are immature, otherwise, T cells are exhausted if ICI is given too late. This work presents theoretical guidance for raising awareness of intervention timing when augmenting ICBT with immune response inducers in clinic.

In uplink grant-free massive multiple-input multiple-output (mMIMO) systems, the performance of available methods for joint user activity and signal detection deteriorates when the correlation of receiving antennas or the number of active devices increases.Moreover, the available methods require the knowledge of noise power, which is often practically unknown.To address the above issues, combining approximate message passing with unitary transformation and expectation maximization algorithm to jointly implement user activity and signal detection was proposed.Different from the conventional approximate message passing algorithm, the proposed one assumes that the noise power was unknown.Firstly, by exploiting the approximate message passing algorithm with unitary transform, the distribution of transmitted symbols together with the distribution of noise power was obtained.Secondly, expectation maximization algorithm was applied to estimate the user activity.Finally, the signal detection was implemented by deriving the posterior distribution of the decoupled signal belongs.Simulation results show that the proposed method is better than the traditional method in joint user activity and signal detection.

Abstract The current dogma in ophthalmology and vision research presumes the intraocular environment to be sterile. However, recent evidence of intestinal bacterial translocation into the bloodstream and many other internal organs including the eyes, found in healthy and diseased animal models, suggests that the intraocular cavity may also be inhabited by a microbial community. Here, we tested intraocular samples from over 1000 human eyes. Using quantitative PCR, negative staining transmission electron microscopy, direct culture, and high-throughput sequencing technologies, we demonstrated the presence of intraocular bacteria. The possibility that the microbiome from these low-biomass communities could be a contamination from other tissues and reagents was carefully evaluated and excluded. We also provide preliminary evidence that a disease-specific microbial signature characterized the intraocular environment of patients with age-related macular degeneration and glaucoma, suggesting that either spontaneous or pathogenic bacterial translocation may be associated with these common sight-threatening conditions. Furthermore, we revealed the presence of an intraocular microbiome in normal eyes from non-human mammals and demonstrated that this varied across species (rat, rabbit, pig, and macaque) and was established after birth. These findings represent the first-ever evidence of intraocular microbiota in humans.

Abstract Background Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of neoplasms with malignant behaviors that can develop from inert slow growth or low malignancy to aggressive metastasis during follow-up. Recently, vimentin and E-cadherin were shown to be prognostic markers in some malignant tumors but were not evaluated in pNETs. The aim of this study was to evaluate the expression and prognostic significance of vimentin and E-cadherin in grade 1 and 2 pNETs. Methods A retrospective review of 227 patients with grade 1 and 2 pNETs undergoing surgical resection was conducted. Tumor specimens were immunohistochemically stained for vimentin and E-cadherin. Correlations between vimentin and E-cadherin expression and other clinicopathological features were then analyzed. Furthermore, overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier and univariate and multivariate Cox regression methods. Results Among 227 patients, 55 (24.2%) harbored tumors with high vimentin expression, while 117 (51.5%) harbored tumors with loss of E-cadherin expression. Patients with high vimentin expression and loss of E-cadherin expression had significantly elevated risks of lymph node metastasis, distant metastasis, perineural invasion and an advanced American Joint Committee on Cancer (AJCC) stage compared with those with low vimentin expression and preserved E-cadherin expression, high vimentin expression and preserved E-cadherin expression, or low vimentin expression and loss of E-cadherin expression. Furthermore, multivariate analysis showed that high vimentin expression with loss of E-cadherin expression was an independent predictor of OS and DFS in patients with grade 1 and 2 pNETs who underwent resection (both P

Suppressing 1/f-shaped low-frequency noise is critical but fundamentally challenging to both electrical and optical transducers. Here, the authors demonstrate a 1/f-noise-free optical sensor with integrated CMOS-compatible heterodyne interferometer and an upconversion amplifying technique, which suppresses the noise by two orders of magnitude.

Low-color-temperature light-emitting diodes (LEDs) (called 1900 K LEDs for short) have the potential to become a healthy light source due to their blue-free property. Our previous research demonstrated that these LEDs posed no harm to retinal cells and even protected the ocular surface. Treatment targeting the retinal pigment epithelium (RPE) is a promising direction for age-related macular degeneration (AMD). Nevertheless, no study has evaluated the protective effects of these LEDs on RPE. Therefore, we used the ARPE-19 cell line and zebrafish to explore the protective effects of 1900 K LEDs. Our results showed that the 1900 K LEDs could increase the cell vitality of ARPE-19 cells at different irradiances, with the most pronounced effect at 10 W/m2. Moreover, the protective effect increased with time. Pretreatment with 1900 K LEDs could protect the RPE from death after hydrogen peroxide (H2O2) damage by reducing reactive oxygen species (ROS) generation and mitochondrial damage caused by H2O2. In addition, we preliminarily demonstrated that irradiation with 1900 K LEDs in zebrafish did not cause retinal damage. To sum up, we provide evidence for the protective effects of 1900 K LEDs on the RPE, laying the foundation for future light therapy using these LEDs.

Abstract Background The prognostic value of external vs internal pancreatic duct stents after pancreaticoduodenectomy remains controversial. This study aimed to evaluate the benefits of external and internal stents using the Fistula Risk Score system with regard to the incidence of clinically relevant postoperative pancreatic fistula. Methods A total of 382 patients who underwent pancreaticoduodenectomy with duct to mucosa pancreaticojejunostomy were retrospectively enrolled from January 2015 to October 2019. The receiver operating characteristic curve was performed for subgroup analysis of the patients at different levels of risk for pancreatic fistula. Results There were no significant differences in terms of pancreatic fistula or other postoperative complications. According to the receiver operating characteristic curve threshold of 3.5, 172 patients with a Fistula Risk Score ≥ 4 and 210 patients with a Fistula Risk Score

Existing multi-band spectrum sensing methods often use the sparsity of broadband spectrum.However, high spectrum occupancy rate of primary users degrades their performance severely.To address this issue, a novel multi-band spectrum sensing method was proposed by exploiting the state correlation among adjacent frequency bands.Firstly, a sticky hidden Markov model (SHMM) was established by regarding the multi-band states and measured energies as hidden and observed variables.In the SHMM, a sticky factor was introduced to represent the state correlation among adjacent frequency bands.Secondly, iterative expressions for the parameters of SHMM were derived.Finally, multi-band spectrum sensing was implemented by obtaining the posterior mean of observations from every frequency bands.Simulation results show that the proposed method outperforms existing methods, and when the false alarm probability is 0.1, the average frequency band occupancy rate is 50%, and the average signal-to-noise ratio is -12 dB, the detection probability can reach close to 0.99, which is about 30% higher than the detection probability of other methods.In addition, the proposed method had a faster convergence rate than existing methods and therefore has lower computational complexity.

Neuromyelitis optica(NMO)is an inflammatory central nervous system(CNS)astrocytic disease with high incidence, neuro-ophthalmic intercross, and humoral immune-dominated in Asian population. It has attracted much attention due to its high pathogenicity, high risk of recurrence, and poor prognosis. It is difficult for patients with NMO-associated optic neuritis(NMO-ON)to benefit from routine treatment, and they are often left with different degrees of optic nerve atrophy. One limitation of the study of NMO-ON is the deficiency of the experimental model. Therefore, the progress and application of NMO and NMO-ON experimental model are reviewed in this paper, aiming to explore the pathological mechanism and possible treatment of NMO visual impairment.

Dry age-related macular degeneration(ARMD)is a degenerative fundus disease whose pathogenesis is not yet fully clear. Dry ARMD with macular pigmentation disorder, drusen and geographic atrophy as main manifestations can lead to irreversible loss of central vision. It's reported that immune and inflammatory reactions play a key role in the development of dry ARMD, in which complement system, pattern recognition receptors, inflammasomes, and various cytokines in immune molecules are closely related to the occurrence of dry ARMD. In this paper, the latest researches on these immune molecules and dry ARMD will be reviewed.

We presented a machine learning-based method to recognize suspension by distinguishing dispersoid-dependent speckle patterns using a convolutional neural network. The dispersoid size and concentration-related transmissive speckle patterns were recorded by a lensless camera when a coherent He-Ne laser irradiated the suspension. Firstly we realized the recognition of the polystyrene microspheres-dispersed suspensions with different particle sizes and the recognition of several common suspensions including protein powder and milk powder with similar concentration. Further recognition from three different food suspensions with unknown concentration was achieved with high accuracy of 99%. The experimental results confirm that this non-contact method could find applications in the measurement and classification of suspension liquid containing micrometers-sized particles.

Duchenne muscular dystrophy (DMD) is an X-linked recessive degenerative disease characterized by progressive weakness of limbs. In this study, we generated an induced pluripotent stem cell line from a DMD patient's dermal fibroblasts with non-integrating Sendai virus. The patient carried a rare c.4518 + 512 T > A variant in the DMD gene. This iPSC line displayed normal iPSC morphology, karyotypes and pluripotency expression markers, and also can be differentiated into the three germ layers.

Abstract Aims/Introduction Safflower yellow (SY) and its main component, hydroxysafflor yellow A, have been demonstrated to show anti‐obesity effects. Peroxisome proliferator‐activated receptor‐γ2 (PPARγ2) is a critical transcription factor in adipose tissue metabolism. The aim of the present study was to explore the effects of SY in high‐fat diet‐induced obese mice, and further investigate the mechanism involving PPARγ2. Methods High‐fat diet‐induced obese mice were given 120 mg/kg/day SY for 8 weeks. Glucose and insulin tolerance tests were carried out. Fat mass and serum levels of glucose and insulin were measured. The expression of insulin signaling pathway‐related genes and PPARγ2 in the adipose tissue was measured. In vitro, the effects of SY (0–500 mg/L) and hydroxysafflor yellow A (0–100 mg/L) on PPARγ2 promoter activities and PPARγ2 messenger ribonucleic acid (mRNA) levels in 3T3‐L1 preadipocytes or adipocytes were also detected. Results Safflower yellow reduced fat mass, decreased glucose levels and improved insulin sensitivity in obese mice. SY also increased the mRNA levels of insulin signaling pathway‐related genes, and increased PPARγ2 mRNA levels by 39.1% in subcutaneous adipose tissue (P

Optic neuritis(ON), which is the blinding optic nerve diseases that the young and middle-aged population are most susceptible to, is an optic neuropathy caused by various factors. Idiopathic optic neuritis(ION)occurs most frequently asmultiple sclerosis related optic neuritis(MS-ON)and neuromyelitis optica related optic neuritis(NMO-ON). ION has the characteristics of acute onset, easy recurrence, and serious dysfunction. Inflammation is an important mechanism of ION. By mediating inflammatory responses and participating in immune responses, proinflammatory cytokines, as one of cytokines which is a general term for a class of small molecule soluble peptides that regulate the immune system, have caused widespread concern in the pathogenesis of ION. This article reviews and discusses researches on the pathogenesis of proinflammatory cytokines-mediated ION at home and abroad in an effort to promote an in-depth study of the pathogenesis, diagnosis and treatment of ION.

Abstract Background To study the morphologic and biochemical changes in the retina and sclera induced by form deprivation high myopia (FDHM) in guinea pigs and explore the possible mechanisms of FDHM formation. Methods Forty 3-week-old guinea pigs were randomized into the blank control (Group I, 20 cases) and model groups (20 cases). In the model group, the right eyes of the guinea pigs were sutured for 8 weeks to induce FDHM (Group II) and the left eyes were considered a self-control group (Group III). The refractive errors were measured with retinoscopy. The anterior chamber depth (AC), lens thickness (L), vitreous chamber depth (V) and axial length (AL) were measured using ultrasonometry A. Retinal and scleral morphology and ultrastructural features were observed with light and electron microscopy. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the retina and sclera were detected with a chemical colorimetric assay. Results After 8 weeks of stitching, the refractive errors of Group II changed from (+ 3.59 ± 0.33) D to (− 7.96 ± 0.55) D, and these values were significantly higher than those of Group I (+ 0.89 ± 0.32) D and Group III (− 0.55 ± 0.49) D (P

Sparse representation based classification method has led to a wide variety of extensions of representation based methods for face recognition. All of these methods partially reveal that collaborative representation is a crucial factor to make sparse representation based classification powerful for face recognition. The collaborative representation based classification (CRC) methods and corresponding variations have achieved effective results in face recognition. For these methods, we found that the test sample has some relevance with the coefficient vector. For example, nonzero elements in the coefficient vector are associated with the classes which the test sample potentially belong to. Exploiting the relevance may obtain sparser coefficient vector in comparison with the traditional methods. Hence, we propose a novel method in which the test sample is closely involved in the solution procedure of optimal coefficient vector. The classification of the proposed method is performed by checking the minimal residual between the test sample and the collaborative representation with respect the test sample of the selected class, which is similar to that of CRC. The proposed method can intensify the corresponding coefficients in the coefficient vector by exploiting the test sample. Experimental results show that the proposed method does achieve more accurate recognition rate.

Mining the correlation has attracted widespread attention in the research community because of its advantages in understanding the dependencies between objects. In this paper, a correlated graph pattern searching scheme has been proposed, that is, provided with a query g as a structured pattern (i.e., a graph), our algorithm is capable of retrieving the top-k graphs that most likely correlated with g. Traditional methods treat graph streams as static records, which is computational infeasible or ineffective because of the complexity of searching correlated patterns in a dynamic graph stream. In this paper, by relying on sliding windows to separate graph streams in chunks, we propose a Hoe-PGPL algorithm to handle the top-k correlated patterns searching from a dynamic perspective. Our algorithm applies Hoeffding bound and twolevel (Sliding window level and local batch level) candidate inspection to discover potential graph candidates and determine the similarity of these candidates without double-checking the previous stream. Theoretical analysis shows that our method can guarantee the quality of the returned answers, and our experiments also present that Hoe-PGPL has an excellent performance with aspects of precision, recall, runtime, and resource consumption.

We investigate the important problem of certifying stability of reinforcement learning policies when interconnected with nonlinear dynamical systems. We show that by regulating the partial gradients of policies, strong guarantees of robust stability can be obtained based on a proposed semidefinite programming feasibility problem. The method is able to certify a large set of stabilizing controllers by exploiting problem-specific structures; furthermore, we analyze and establish its (non)conservatism. Empirical evaluations on two decentralized control tasks, namely multi-flight formation and power system frequency regulation, demonstrate that the reinforcement learning agents can have high performance within the stability-certified parameter space and also exhibit stable learning behaviors in the long run.

Study of the vibration mechanisms of transformer windings may lead to useful applications of vibration techniques to transformer online diagnosis. In a power transformer, the clamping force provides a boundary mechanical constraint to ensure the integrity of the winding. Thus, the looseness of the clamping force is an important health indicator for a transformer. Although the effect of clamping force on a winding's stiffness and natural frequencies is known, the effect of time-varying load current on these natural frequencies remains unsolved. In this paper, this effect is investigated by studying the mechanical frequency response function of an on-load single-phase winding under different clamping forces and variation of the harmonic amplitude of in-service transformers with load current. Then, a gated recurrent unit (GRU) neural network is used to explore the relationship between current sequence and vibration sequence for operating transformers. This study shows that the electromagnetic force induced by the load current affects the vibration response of the winding structure, especially when the looseness of the clamping force is significant. A potential application of the observed phenomenon for online detection of winding conditions is also illustrated.

Sirtuin 4 (SIRT4) is one of seven mammalian sirtuins that possesses ADP-ribosyltransferase, lipoamidase and deacylase activities and plays indispensable role in metabolic regulation. However, the role of SIRT4 in the retina is not clearly understood. The purpose of this study was to explore the location and function of SIRT4 in the retina. Therefore, immunofluorescence was used to analyze the localization of SIRT4 in rat, mouse and human retinas. Western blotting was used to assess SIRT4 and glutamine synthetase (GS) protein expression at different developmental stages in C57BL/6 mice retinas. We further analyzed the retinal structure, electrophysiological function and the expression of GS protein in SIRT4-deficient mice. Excitotoxicity was caused by intravitreal injection of glutamate (50 nmol) in mice with long-term intraperitoneal injection of resveratrol (20 mg/Kg), and then retinas were subjected to Western blotting and paraffin section staining to analyze the effect of SIRT4 on excitotoxicity. We show that SIRT4 co-locates with Müller glial cell markers (GS and vimentin). The protein expression pattern of SIRT4 was similar to that of GS, and both increased with development. There were no significant retinal structure or electrophysiological function changes in 2-month SIRT4-deficient mice, while the expression of GS protein was decreased. Moreover, long-term administration of resveratrol can upregulate the expression of SIRT4 and GS while reducing the retinal injury caused by excessive glutamate. These results suggest that SIRT4 is highly expressed in retinal Müller glial cells and is relevant to the expression of GS. SIRT4 does not appear to be essential in retinal development, but resveratrol, as an activator of SIRT4, can upregulate GS protein expression and protect the retina from excitotoxicity.

This paper is concerned with an analysis of the electrical conductivity of graphene/cement composites by means of DC (direct current) and AC (alternating current) techniques. Moreover, the micrograph and element composition of composites have been characterized through SEM (scanning electron microscopy) and EDS (energy-dispersive spectrometers) techniques, respectively. Results revealed that a percolation transition region Φ2–Φ1 (Φ2 and Φ1 values are determined as 0.8% and 1.8%, respectively) can be observed in the S-shaped curve. In addition, the logistic model has been recommended to characterize the relationship between the conductivity and the graphene concentration, which ranged from 0.001% to 2.5%. The micrographs obtained by SEM technique clearly indicate a complete conductive network as well as agglomeration of graphene slices when the graphene content reaches the threshold value. Furthermore, graphene slices can be distinguished from the cement hydration products by means of the analysis of element composition obtained through the EDS technique. It is promising to apply the graphene/cement composites as intelligent materials.

This paper reports a series of experimental and modeling investigations on two piezoelectric arrays made of polyvinylidene fluoride (PVDF) films. They were embedded inside rubber cylinders and used to directly measure the internal stresses generated by various external excitations applied to the top surface of the cylinder. Corresponding finite element (FE) models were established to reveal the relationship between the PVDF output and the stress field applied to it. This research improves the understanding of the output mechanism of the embedded PVDF and provides useful information for the design of PVDF sensors.

Retinal pigmentosa(RP)is a hereditary blinding retinal disease whose pathogenesis is not fully understand. It is characterized by night blindness, progressive narrowing visual field and vision decreased. Bone spicule-shaped pigment,retinal vessel attenuation and pallor optic disc can be seen at the fundus.RP is geneticallyand phenotypically heterogeneous, autosomal recessive retinitis pigmentosa accounts for 5%-20% of RP. There are 43 pathogenic genes have been mapped in autosomal recessive retinitis pigmentosa(ARRP), 40 of them have been cloned, and new related pathogenic genes have been reporting. This article reviewsthe newest progress of the research in AGBL5, ARHGEF18, HGSNAT and ZNF408 gene relevant to ARRP.

As an essential element for the diagnosis and rehabilitation of psychiatric disorders, the electroencephalogram (EEG) based emotion recognition has achieved significant progress due to its high precision and reliability. However, one obstacle to practicality lies in the variability between subjects and sessions. Although several studies have adopted domain adaptation (DA) approaches to tackle this problem, most of them treat multiple EEG data from different subjects and sessions together as a single source domain for transfer, which either fails to satisfy the assumption of domain adaptation that the source has a certain marginal distribution, or increases the difficulty of adaptation. We therefore propose the multi-source marginal distribution adaptation (MS-MDA) for EEG emotion recognition, which takes both domain-invariant and domain-specific features into consideration. First, we assume that different EEG data share the same low-level features, then we construct independent branches for multiple EEG data source domains to adopt one-to-one domain adaptation and extract domain-specific features. Finally, the inference is made by multiple branches. We evaluate our method on SEED and SEED-IV for recognizing three and four emotions, respectively. Experimental results show that the MS-MDA outperforms the comparison methods and state-of-the-art models in cross-session and cross-subject transfer scenarios in our settings. Codes at https://github.com/VoiceBeer/MS-MDA.

Aiming at the problem of low-altitude windshear wind speed estimation for airborne weather radar without independent identically distributed (IID) training samples, this paper proposes a low-altitude windshear wind speed estimation method based on knowledge-aided sparse iterative covariance-based estimation STAP (KASPICE-STAP). Firstly, a clutter dictionary composed of clutter space–time steering vectors is constructed using prior knowledge of the distribution position of ground clutter echo signals in the space–time spectrum. Secondly, the SPICE algorithm is used to obtain the clutter covariance matrix iteratively. Finally, the STAP processor is designed to eliminate the ground clutter echo signal, and the wind speed is estimated after eliminating the ground clutter echo signal. The simulation results show that the proposed method can accurately realize a low-altitude windshear wind speed estimation without IID training samples.

ObjectiveWe investigated lenvatinib plus programmed cell death-1 (PD-1) inhibitors as a first-line treatment for initially unresectable biliary tract cancer (BTC).MethodsIn this Phase II study, adults with initially unresectable BTC received lenvatinib (body weight ≥60 kg, 12 mg;

The lakes at the southern Mongolian Plateau are sensitive to the variation of EASM changes during the Holocene, and hence the lacustrine records of these lakes provide prospects for understanding how lake environmental changes respond to EASM variation at different timescales. The interpretation of proxy indexes of lacustrine sediments is complex due to the various climatic or/and environmental factors influencing the processes during deposition and after deposition. In this study, the elements and colors of an 11.7-m lacustrine record from Chagan Nur at the southern Mongolian Plateau of northern China were analyzed to constrain the lake environmental changes during the Holocene. The results show that stable elements of Al, Si, K, Ti, Fe, and Rb are more related to surface erosion or/and vegetation coverage, and the variation of Sr is related to the lake-level change in Chagan Nur. The element and color of the lacustrine records show that a small and shallow lake environment occurred at Chagan Nur during 11.7–10.5 ka, the lake level had increased during 10.5–7 ka, and then the lake shrank with strength surface erosion during 7–6.2 ka and from 2 ka to the present. The lake level and surface erosion changes of Chagan Nur have shown a direct response to EASM precipitation changes as reconstructed from the pollen record from the Chagan Nur Lake and other records from northern China.

ObjectivesTo reveal the mechanisms of the effects of mortalin in hepatocellular carcinoma (HCC) and to identify potential novel chemical inhibitors of mortalin.Materials and MethodsFor the experiments, three HCC cell lines (HepG2 cells, Hep3B cells, and sorafenib-resistant HuH7 cells) and xenografted nude mice were used. For the clinical analysis, cohorts of 126 patients with HCC and 34 patients with advanced recurrent HCC receiving sorafenib therapy were examined.ResultsMortalin regulated the phosphorylation-modification of cancer-associated proteins and also regulated angiogenesis-related secretome to cause angiogenesis and sorafenib resistance in HCC cells. Two molecular mechanisms were identified. In one, via phosphatidylinositol 3-kinase (PI3K)/Akt signaling, mortalin regulated nuclear factor (NF)-κB and then activated vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR)2 and granulocyte-macrophage colony-stimulating factor (GM-CSF), leading to neovascularization. In the other, mortalin regulated PI3K/Akt/β-catenin and then regulated Bcl-XL and Bcl-2, leading to the antiapoptosis effect of HCC. Treatment of the sorafenib-resistant xenografts with sorafenib in combination with mortalin knockdown facilitated the sorafenib-mediated inhibition of tumor growth and angiogenesis and increased apoptosis. Mortalin was a potential risk factor for HCC, predicting poor prognosis and sorafenib resistance. Finally, we showed that caffeic acid (C9H8O4) could bind to and induce the ubiquitination-mediated degradation of mortalin, which in turn blocked the abovementioned signaling pathways, leading to the inhibition of angiogenesis and the reversal of sorafenib resistance.ConclusionsMortalin, which regulates the phosphorylation of cancer-associated proteins, caused angiogenesis and sorafenib resistance, and was a competitive risk factor for HCC. Caffeic acid can therefore be considered a novel chemical inhibitor that targets the action of mortalin and a potential treatment for HCC.

Myopic population of China is already nearly 600 million, the rate of teenager myopic occupies the first place in the world, myopia hsa already became one of the main diseases that endangers our adolescent's health. Dopamine is the main catecholamine in retina. Many studies have found that increasing the content of dopamine can effectively inhibit the development of myopia. Form-deprivation myopia is a classical method of myopia modeling. By observing the influence of dopamine and its receptors on the development of form-deprivation myopia, its role in the development of myopia can be reflected, and it is of great significance to guide and control the occurrence and development of myopia. In this paper, the effects of dopamine and its receptors on the development of form-deprivation myopia were reviewed in order to provide reference for the prevention and treatment of myopia.

AIM: To establish a model of retinal neurodegeneration induced by N-Methyl-D-aspartic acid (NMDA) in adult zebrafish. METHODS: We compared the effects of three different NMDA delivery methods on retinal neurodegeneration in adult zebrafish: immersion (I.M.), intravitreal injection (I.V.), and intraperitoneal injection (I.P.), and examined retinal pathology and degeneration by hematoxylin and eosin and TUNEL staining in the treated zebrafish. Effects of the NMDA receptor antagonist MK-801 and the natural product resveratrol on NMDA-induced retinal neurodegeneration were also assessed. RESULTS: The thickened inner retina was seen in histology with 100 μmol/L NMDA by I.M. administration. Significant apoptosis in the retinal ganglion cell layer and retinal thickness reduction occurred in 0.5 mol/L NMDA I.P. administration group.Seizure-like behavioral changes, but no retinal histological alteration occurred in 16 mg/kg NMDA I.P. administration group. Resveratrol and MK-801 prevented NMDA-induced retinal neurodegeneration in the zebrafish. CONCLUSION: Among the three drug administration methods, I.V. injection of NMDA is the most suitable for establishment of an acute retinal damage model in zebrafish. I.M. with NMDA is likely the best for use as a chronic retinal damage model. I.P. treatment with NMDA causes brain damage. Resveratrol and MK801 may be a clinically valuable treatment for retinal neurodegeneration.

Angiotensin I converting enzyme (ACE) gene is one of the most-studied candidate genes related to essential hypertension (EH). Pulse pressure (PP) may reflect vascular stiffness, especially in patients with EH, and has been used to predict EH. Previous evidence has indicated that obesity is a traditional risk factor of hypertension. The aim of the present study was to investigate the interaction between the obesity status and ACE gene polymorphisms on the development of high level of PP. A total of 1980 adults (1024 hypertensive and 956 normotensive) were included in this study and genotyped for ACE gene polymorphisms. The results showed that rs4343 and rs4351 in ACE gene were risk factors of high level of pulse pressure (p < 0.05). We also detected positive interactions between the two SNPs and obesity status in the pathway of high level PP.

A tapered asymmetric directional coupler is considered as a promising structure for high tolerance and efficient on-chip mode (de)multiplexers. However, the optimum geometry parameters selection still remains empirical without specific numerical guidance. Here, an in-depth analysis has been carried out based on coupling mode theory. A theoretical model is built aiming to combine the consideration of device efficiency, mode crosstalk and fabrication tolerance. According to that, mode (de)multiplexers (TE0-TE1, TE0-TE2, TM0-TM1, TM0-TM2) with broad operation wavelength (C + L band) and low mode crosstalk (minimum -30 dB) are fabricated. The proposed theoretical model can serve as a guideline for the design and optimization of the tapered ADC based mode (de)multiplexers.

In this paper, a new direction-of-arrival (DOA) estimation method based on multiple Toeplitz matrices reconstruction is proposed for coherent narrowband signals with a uniform linear array (ULA). First, the received signals impinging on the ULA are rearranged in a Toeplitz matrix, and a full set of correlation matrices are computed by the Toeplitz-based matrix and the observed data of each sensor. Then, a weighted summation by squaring these correlation matrices is obtained to form the full rank equivalent data covariance matrix. Furthermore, a forward-and-backward scheme is presented to improve the estimation accuracy of the covariance matrix. Based on the joint diagonalization structure of the covariance matrix with noise contributions as a scalar matrix, the angle estimation problem can be resolved by combining it with subspace-based methods. In comparison with currently known matrix reconstruction methods, the proposed algorithm applies all information contained in the correlation matrices adequately without de-noising processing in advance. Even in the case of a low signal-to-noise ratio and low snapshot number with half the array aperture reduced, the new method provides good performance on estimation and resolution. Finally, simulation results are demonstrated to verify the theoretical prediction.

When used for direction of arrival (DOA) estimation with large uniform linear arrays (ULAs), both root-MUSIC and unitary root-MUSIC (U-root-MUSIC) involve high-dimension eigenvalue decomposition (EVD) and high-degree polynomial rooting computations. In this paper, we propose a novel real-valued modification of root-MUSIC to reduce the computational complexity. We first divide the large ULA into two moderate subarrays and exploit the subarray structure to extract a real noise matrix with reduced-dimension EVD. Using this real noise matrix, we construct a real polynomial, and further employ a variable substitution technique to transform the real polynomial to a new one with reduced degree equivalently. As such, both tasks of EVD and polynomial rooting can be computed efficiently. We finally show by numerical simulations that with significantly reduced computational complexity, the proposed method sacrifices statistically nonsignificant accuracy that is acceptable.

Besides the ID class features, the advertisement click log file contains many significant features, which make the study of the advertisement clickthrough rate prediction more difficult. In this study, we convert original features into numerical meaningful ones, which reduce the sparsity and redundancy. In order to solve the problem of class imbalance, we propose a downsampling algorithm based on K-means model to classify large samples, then divide them into some sensible and rational features by the heuristic methods. To further improve the feature representation, we finally select and combine features by the Gradient Boosting Decision Tree model and process high-dimensional features by the logistic regression method. We conducted experiments on the dataset of Tencent SOSO and demonstrated that our approach outperforms the state-of-the-art baseline methods by 0.05% on average in terms of R2 and by 50.5% on average in terms of RMSE.

With the popularity of Bitcoin, there is a greater demand for the scalability of the Bitcoin blockchain, which is susceptible to the efficiency of block propagation. In the Bitcoin blockchain, efficient block propagation approach can reduce the computing power and the risk of forks. Meanwhile, larger blocks help to improve the throughput of transactions. Thus, the block propagation is a major issue of the scalability of the Bitcoin network. This paper introduces a method to reduce the required bandwidth of block propagation with erasure coding. To begin with, the network nodes are classified into several clusters. When a node wants to propagate a block, the node does not need to propagate the whole information of the block. Instead, the node can only transmit the transaction IDs and the coded information to each cluster. The simulation shows that the proposed method can significantly ease the network traffic among these clusters.

A novel real-valued algorithm of the popular root multiple signal classification of non-circular sources (NC-root-MUSIC) is developed for low-complexity direction of arrival (DOA) estimation. The proposed real-valued NC-root-MUSIC (RV-NC-root-MUSIC) reduces the computational burden mainly in following three aspects. First, unlike the classical real-valued algorithms, such as unitary transform, the complex-valued operation is still implemented when acquiring DOAs. However, the proposed RV-NC-root-MUSIC implements real-valued received data. Therefore, both tasks of eigenvalue decomposition (EVD) (or singular value decomposition (SVD)) and polynomial rooting can be implemented completely by real-valued computations in the proposed RV-NC-root-MUSIC. Next, due to the conjugate expansion of the non-circular sources, the steering vector dimension is extended by a factor of two, and the real-valued signal- and noise-subspace can be calculated by two reduced-dimension sub-matrices. As such, large-scale EVD/SVD computation is avoided. Finally, a real coefficient rooting polynomial with a similar order as NC-root-MUSIC is constructed. A variable substitution technique is further proposed to reduce the degree of this polynomial by half without sacrificing accuracy, which allows fast coefficient computation and real-valued rooting. The real-valued computation and reduced-order polynomial rooting in the proposed method result in a significant reduction in computational cost as compared to state-of-the-art methods. Numerical computer simulations illustrate that with significantly reduced complexity, the fast RV-NC-root-MUSIC algorithm can provide similar root mean square errors (RMSE) close to the conventional methods.

AIM: To research the clinical effects of visual display terminal(VDT)syndrome after local treatment near the eyes in combination with systemic comprehensive treatment.METHODS: Totally 62 patients(124 eyes)with VDT syndrome were randomly divided into a trial group and a control group, 31 cases(62 eyes)in each group. In the control group, artificial tears as eye drops were given. In addition to the above local treatment with artificial tears, the trial group was also treated with the auricular acupressure and tuina at the acupoints near orbits and the whole body. A health education was carried out in both of the two groups. The course of the treatment of the two groups was 2wk. The symptomatic scores, and the amplitude of accommodation, facility of accommodation, accommodative response, near point of convergence and the ratio of accommodative convergence to accommodation(AC/A)based on refractive error correction of all the patients were detected before and after the treatment. The parameters gained before and after the treatment were compared for evaluating efficacy. RESULTS: After treatment, the symptomatic scores and facility of accommodation of the two groups were significantly improved compared with those before treatment(PPCONCLUSION: Local treatment near the eyes in combination with systemic comprehensive treatment can effectively improve the accommodative and convergent functions of patients with VDT syndrome, and relieve their symptoms of asthenopia and fatigue.

Müller glial cells (MGCs) are a group of glial cells in the retina that provide essential support to retinal neurons; however, the understanding of MGC apoptosis and autophagy remains limited. This study was aimed at investigating the role of autophagy in MGCs under normal and oxidative conditions, and identifying the underlying mechanisms. In addition, the sirtuin 4 (SIRT4)-mediated signaling pathway was observed to regulate the autophagic process in MGCs. To assess the effect of autophagy on MGC mitochondrial function and survival, we treated rMC-1 cells—rat-derived Müller glial cells—with rapamycin and 3-methyladenine (3-MA), and found that MGC death was not induced by such treatment, while autophagic dysfunction could increase MGC apoptosis under oxidative stress, as reflected by the expression level of cleaved caspase 3 and PI staining. In addition, the downregulation of autophagy by 3-MA could influence the morphology of the mitochondrial network structure, the mitochondrial membrane potential, and generation of reactive oxygen species (ROS) under oxidative stress. Moreover, SIRT4 depletion enhanced autophagosome formation, as verified by an increase in the LC3 II/I ratio and a decrease in the expression of SQSTM1/p62, and vice versa. The inhibition of AMPK phosphorylation by compound C could reverse these changes in LC3 II/I and SQSTM1/p62 caused by SIRT4 knockdown. Our research concludes that MGCs can endure autophagic dysfunction in the absence of oxidative stress, while the downregulation of autophagy can cause MGCs to become more sensitized to oxidative stress. Simultaneous exposure to oxidative stress and autophagic dysfunction in MGCs can result in a pronounced impairment of cell survival. Mechanically, SIRT4 depletion can activate the autophagic process in MGCs by regulating the AMPK–mTOR signaling pathway.

Abstract Background Multi-drug resistance (MDR) is one of the main obstacles for treatment of advanced/recurrent hepatocellular carcinoma (HCC). We have previously identified arsenic trioxide (ATO) as an effective metastasis/angiogenesis inhibitor in HCC. Here, we further found that MDR-HCC cells were more sensitive to ATO. Methods The MDR-HCC cells were used as experimental models. Biological functions were investigated using cell transfection, polymerase chain reaction, western blot, southwestern blot, immunostaining, immunoprecipitation plus atomic fluorescence spectrometry, and so on. Results The MDR-HCC cells underwent high oxidative stress condition, and employed adaptive mechanisms for them to survive; while ATO abolished such mechanisms via targeting the 14–3-3η/nuclear factor kappa B (NF-κB) feedback Loop. Briefly, in MDR cells, the increase of ROS activated NF-κB signaling, which transcriptionally activated 14–3-3η. Meanwhile, the activation of NF-κB can be constitutively maintained by 14–3-3η. As a NF-κB inhibitor, ATO transcriptionally inhibited the 14–3-3η mRNA level. Meanwhile, ATO was also validated to directly bind to 14–3-3η, enhancing the degradation of 14–3-3η protein in an ubiquitination-dependent manner. Knockdown of 14–3-3η reduced the ATO-induced reversal extents of drug resistance in MDR cells. Conclusion 14–3-3η/NF-κB feedback loop plays an important role in maintaining the MDR phenotype in HCC. Moreover, via targeting such feedback loop, ATO could be considered as a potential molecular targeted agent for the treatment of HCC.

Abstract Background Patients with locally advanced rectal cancer (LARC) achieving a pathological complete response (pCR) to neoadjuvant treatment usually have a good prognosis, but only accounted for less than 20%. Case presentation We report a case of a 25-year-old male with LARC treated with neoadjuvant FOLFOX chemotherapy, and experienced a pCR. The next-generation sequencing analysis revealed the presence of breast cancer gene 2 (BRCA2) somatic mutation and an increased somatic mutational load without microsatellite instability (MSI). To our knowledge, this is the first report of BRCA2 mutant LARC that demonstrated significant benefit from FOLFOX neoadjuvant treatment. Conclusions This case indicated an association of BRCA2 mutation with high mutation loads and an excellent response of oxaliplatin-based chemotherapy regimen for LARC. Our findings encourage further studies to analyze BRCA mutations in patients with LARC, especially for those patients unable or unwilling to receive radiotherapy.

Becker muscular dystrophy (BMD) is an X-linked recessive muscular disorder caused by mutations in the dystrophin. We generated a human iPSC line from peripheral blood mononuclear cells (PBMCs) of a patient with duplications of exons 2-19 in the dystrophin. The PBMCs were reprogrammed using the episomal reprogramming plasmids contained a combination of expressions of human OCT4, SOX2, NANOG, LIN28, C-MYC, KLF4 and SV40LT. We conducted the tests on the iPSCs including Karyotype analysis, expressed pluripotency markers and teratoma forming three germ layers. The iPSC line is a useful cell model to further research on genetic treatment or new therapeutic drugs.

Bovine herpesvirus type I (BoHV-1) is an important pathogen that causes respiratory disease in bovines. The disease is prevalent worldwide, causing huge economic losses to the cattle industry. Gene-deficient vaccines with immunological markers to distinguish them from wild-type infections have become a mainstream in vaccine research and development. In order to knock out the gE gene BoHV-1, we employed the CRISPR/Cas9 system. Interesting phenomena were observed at the single guide RNA (sgRNA) splicing site, including gene insertion, gene deletion, and the inversion of 5′ and 3′ ends of the sgRNA splicing site. In addition to the deletion of the gE gene, the US9 gene, and the non-coding regions of gE and US9, it was found that the US4 sequence, US6 sequence, and part of the US7 sequence were inserted into the EGFP sgRNA splicing site and the 3′ end of the EGFP sequence was deleted. Similar to the BoHV-1 parent, the BoHV-1 mutants induced high neutralizing antibodies titer levels in mice. In summary, we developed a series of recombinant gE-deletion BoHV-1 samples using the CRISPR/Cas9 gene editing system. The mutant viruses with EGFP+ or EGFP− will lay the foundation for research on BoHV-1 and vaccine development in the future.

Introduction Neuromyelitis optica spectrum disorders (NMOSD) is an inflammatory and heterogeneous astrocyte disorder of the central nervous system with the characteristic of higher incidence in women and Asian people. Most patients with NMOSD have a course of recurrence and remission that is prone to cause paralysis and blindness. Several studies have confirmed the efficacy and promising prospect of mycophenolate mofetil (MMF) in the treatment of NMOSD. Yet its therapeutic effect and safety are controversial. Although there has been two published literature that is relevant to the topic of this study, both of them have certain defects, and they can only provide answers about the efficacy or safety of MMF in the treatment of NMOSD from partial perspectives or conclusions. This research aims to perform a direct and comprehensive systematic review and meta-analysis to evaluate MMF’s effectiveness and safety in treating NMOSD.Methods and analysis This systematic review will cover all comparative researches, from randomised controlled trials to cohort studies, and case–control study. A relevant literature search will be conducted in PubMed, Web of Science, EMBASE, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database and Chinese Biomedical Literature Database from their inception to 31 June 2020. We will also search registers of clinical trials, potential grey literature and abstracts from conferences. There are no limits on language and publication status. The reporting quality and risk of bias will be assessed by two researchers independently. Expanded Disability Status Scales and annualised relapse rate will be evaluated as the primary outcome. The secondary outcomes will consist of the frequency and severity of adverse events, best-corrected visual acuity, relapse-free rate and time to the next attack. A meta-analysis will be performed using RevMan V.5.3 software provided by the Cochrane Collaboration and Stata V.12.0.Ethics and dissemination Because the data used for this systematic review will be exclusively extracted from published studies, ethical approval and informed consent of patients will not be required. The systematic review will be published in a peer-reviewed journal, presented at conferences and will be shared on social media platforms.PROSPERO registration number CRD42020164179.

Temperature distribution in concrete is significant to the concrete structure’s macro properties and different factors affect the heat transfer in concrete, and therefore influence the temperature distribution. This work established a three-dimensional transient heat transfer model coupled with various environmental factors, using the finite element method for calculating the results and real-measured data for testing accuracy. In addition, a sensitivity evaluation of various factors was conducted. Due to various environmental factors, the results revealed that the prediction of temperature distribution in concrete by the three-dimensional model had great accuracy with an error of less than 4%. A particular hysteresis effect of temperature response in the concrete existed. Considering heat transfer in different spatial directions, the model can predict the temperature change of each spatial point instead of the spatial surface in different depths, proving the shortcomings of a one-dimensional heat transfer model. A greater solar radiation intensity caused a more significant temperature difference on the concrete surface: the surface temperature difference in July was twice as significant as that in December. Wind speed had a cooling effect on the concrete surface, and stronger wind speed accompanied with a stronger cooling effect made the surface temperature closer to the ambient temperature. Material properties had different effects on the temperature distribution of the surface part and internal part: the specific heat capacity determined the speed of the outer layer temperature change while the thermal conductivity determined the speed of the inner layer temperature change.

Babies who are born small for their gestational age (SGA) have low iron reserves, thus probably increasing the risk of offspring anemia. We studied two longitudinal birth cohorts to evaluate the association of SGA with the risk of anemia during early childhood. Cohort 1 was recruited from five counties in northern China involving 17,180 singleton infants born during 2006–2009 and cohort 2 from 21 counties or cities in southern China involving 180,619 children born during 1993–1996. Anemia was diagnosed by hemoglobin at 6 and 12 months in cohort 1 and at 55 months in cohort 2. The overall incidences of SGA were 7.07% and 5.73% in cohort 1 and cohort 2, respectively. SGA was associated with increased anemia at 6 months (adjusted odds ratio (OR): 1.52; 95% confidence interval (CI): 1.24, 1.86) and 12 months (adjusted OR: 1.42; 95% CI: 1.13, 1.79) in cohort 1 and at 55 months (adjusted OR: 1.11; 95% CI: 1.05, 1.17) in cohort 2. The positive associations for anemia at 6, 12, and 55 months persisted in both logistics and multiple linear models. Our results support a gradually decreased association between SGA and the increased risk of childhood anemia with a longer follow-up time in infants and children.

As an important optoelectronic integration platform, silicon photonics has achieved significant progress in recent years, demonstrating the advantages on low power consumption, low cost, and complementary metal–oxide–semiconductor (CMOS) compatibility. Among the different silicon photonics devices, the silicon electro-optic modulator is a key active component to implement the conversion of electric signal to optical signal. However, conventional silicon Mach–Zehnder modulators and silicon micro-ring modulators both have their own limitations, which will limit their use in future systems. For example, the conventional silicon Mach–Zehnder modulators are hindered by large footprint, while the silicon micro-ring modulators have narrow optical bandwidth and high temperature sensitivity. Therefore, developing a new structure for silicon modulators to improve the performance is a crucial research direction in silicon photonics. Meanwhile, slow-light effect is an important physical phenomenon that can reduce the group velocity of light. Applying slow-light effect on silicon modulators through photonics crystal and waveguide grating structures is an attractive research point, especially in the aspect of reducing the device footprint. In this paper, we review the recent progress of silicon-based slow-light electro-optic modulators towards future communication requirements. Beginning from the principle of slow-light effect, we summarize the research of silicon photonic crystal modulators and silicon waveguide grating modulators in detail. Simultaneously, the experimental results of representative silicon slow-light modulators are compared and analyzed. Finally, we discuss the existing challenges and development directions of silicon-based slow-light electro-optic modulators for the practical applications.